The objectives of this research project are to use biochemical and population genetic principles to define the genetic heterogeneity of human lysosomal acid lipase (LAL) and to determine whether genetic variation of this enzyme alters one's risk of developing atherosclerosis. Wolman's disease and cholesteryl ester storage disease result from genetically determined deficiency of LAL, and both appear to have associated premature atherosclerosis. Using fluorometric assay of LAL, and adapting it to the electrophoretic identification of the enzyme, the investigators have developed methods for the detection of LAL isozymes, one of which is absent in Wolman's and cholesteryl ester storage disease. These methods have been adapted to the study of peripheral lymphocytes. A survey of LAL in lymphocytes of randomly-sampled individuals will be made to define the heterogeneity of LAL in the population. Family studies of LAL will be done to determine whether this heterogeneity is under genetic control and what the nature of the genetic control is. Patients with documented atherosclerosis, and their families, will be tested to determine whether their disease is correlated with one or more of the LAL variants. In addition, physical and biochemical properties of LAL variants will be characterized.